Evaluation of O -[18 F]fluoromethyl- d -tyrosine as a radiotracer for tumor imaging with positron emission tomography

• Published in: Nuclear medicine and biology 2009-04, Vol.36 (3), p.295-303
• Main Authors: Urakami, Takeo, Sakai, Koichi, Asai, Tomohiro, Fukumoto, Dai, Tsukada, Hideo, Oku, Naoto
• Format: Article
• Language: English
• Subjects: Animals; Biological Transport; Cell Line, Tumor; Humans; Male; Mice; Mice, Inbred BALB C; Neoplasms - diagnostic imaging; Neoplasms - metabolism; Positron-Emission Tomography; Radioactive Tracers; Radiology; Rats; Rats, Inbred F344; Staining and Labeling; Stereoisomerism; Tyrosine - analogs & derivatives; Tyrosine - chemistry; Tyrosine - metabolism
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2008.12.012

Abstract O -[18 F]Fluoromethyl- d- tyrosine ( d -[18 F]FMT) has been reported as a potential tumor-detecting agent for positron emission tomography (PET). However, the reason why d -[18 F]FMT is better than l -[18 F]FMT is unclear. To clarify this point, we examined the mechanism of their transport and their suitability for tumor detection. The stereo-selective uptake and release of enantiomerically pure d - and l -[18 F]FMT by rat C6 glioma cells and human cervix adenocarcinoma HeLa cells were examined. The results of a competitive inhibition study using various amino acids and a selective inhibitor for transport system L suggested that d -[18 F]FMT, as well as l -[18 F]FMT, was transported via system L, the large neutral amino acid transporter, possibly via LAT1. The in vivo distribution of both [18 F]FMT and [18 F]FDG in tumor-bearing mice and rats was imaged with a high-resolution small-animal PET system. In vivo PET imaging of d -[18 F]FMT in mouse xenograft and rat allograft tumor models showed high contrast with a low background, especially in the abdominal and brain region. The results of our in vitro and in vivo studies indicate that l -[18 F]FMT and d -[18 F]FMT are specifically taken up by tumor cells via system L. d -[18 F]FMT, however, provides a better tumor-to-background contrast with a tumor/background (contralateral region) ratio of 2.741 vs. 1.878 with the l -isomer, whose difference appears to be caused by a difference in the influence of extracellular amino acids on the uptake and excretion of these two isomers in various organs. Therefore, d -[18 F]FMT would be a more powerful tool as a tumor-detecting agent for PET, especially for the imaging of a brain cancer and an abdominal cancer.